In:
Angewandte Chemie, Wiley, Vol. 130, No. 1 ( 2018-01-02), p. 293-297
Abstract:
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides containing dichloro(1,10‐phenanthroline)copper(II) and various organelle‐targeting peptide sequences is reported. The mitochondria‐targeting metallopeptide 1 exploits the higher mitochondrial load in breast CSCs over the corresponding non‐CSCs and the vulnerability of breast CSCs to mitochondrial damage to potently and selectively kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC‐potent agent. Mechanistic studies show that 1 enters CSC mitochondria, induces mitochondrial dysfunction, generates reactive oxygen species (ROS), activates JNK and p38 pathways, and prompts apoptosis. To the best of our knowledge, 1 is the first metallopeptide to selectivity kill breast CSCs in vitro.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.201710910
Language:
English
Publisher:
Wiley
Publication Date:
2018
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